Synthesis of indolylmaleimides
The present invention provides a method for synthesizing indolylmaleimides by reacting an activated maleimide preferably with an optionally substituted organometallic-3-indole in the presence of a transition metal catalyst.
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Claims
1. An indolylmaleimide of the formula: ##STR33## wherein R.sup.3 is --H or a protecting group, R.sup.11 's are hydrogen or up to four substituents independently selected from halo, C.sub.1 to C.sub.4 alkyl, hydroxy, C.sub.1 to C.sub.4 alkoxy, halo, C.sub.1 to C.sub.4 -alkyl, nitro, --NHCO(C.sub.1 -C.sub.4 alkyl) and --NR.sup.9 R.sup.10 where R.sup.9 and R.sup.10 are independently hydrogen or methyl, R.sup.12 is an --NH protective group and R.sup.14 is hydrogen or an optionally substituted alkyl.
2. The indolylmaleimide of claim 1 wherein R.sup.12 is selected from the group consisting of trimethylsilylethoxymethyl, benzyl, and tosyl, or wherein R.sup.12 together with the indole N forms a carbamate, an amide, an alkyl sulfonamide or an aryl sulfonamide.
3. The indolylmaleimide of claim 1 wherein R.sup.11 is hydrogen.
4. The indolylmaleimide of claim 1 wherein R.sup.14 is hydrogen.
5. The indolylmaleimide of claim 1 wherein R.sup.12 is methyl.
6. The indolylmaleimide of claim 1 wherein R.sup.11 and R.sup.14 are hydrogen and R.sup.12 is methyl.
7. The indolylmaleimide of the formula: ##STR34## wherein R.sup.3 is --H or methyl, R.sup.11 's are hydrogen or up to four substituents independently selected from halo, C.sub.1 to C.sub.4 alkyl, hydroxy, C.sub.1 to C.sub.4 alkoxy, halo, C, to C.sub.4 -alkyl, nitro, --NHCO(C.sub.1 -C.sub.4 alkyl) and --NR.sup.9 R.sup.10 where R.sup.9 and R.sup.10 are independently, hydrogen or methyl, R.sup.12 is selected from the group consisting of trimethylsilylethoxymethyl benzyl, and tosyl, or wherein R.sup.12 together with the indole N forms a carbamate, an amide, an alkyl sulfonamide or an aryl sulfonamide and R.sup.14 is hydrogen or an optionally substituted alkyl.
8. The indolylmaleimide of claim 7 wherein R.sup.11 is hydrogen.
9. The indolylmaleimide of claim 7 wherein R.sup.11 is hydrogen.
10. The indolylmaleimide of claim 7 wherein R.sup.12 is methyl.
11. The indolylmaleimide of claim 7 wherein R.sup.11 and R.sup.14 are hydrogen and R.sup.12 is methyl.
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Type: Grant
Filed: Dec 19, 1997
Date of Patent: Jan 12, 1999
Assignee: Eli Lilly and Company (Indianapolis, IN)
Inventors: Margaret M. Faul (Zionsville, IN), Michael R. Jirousek (Indianapolis, IN), John H. McDonald, III (Carmel, IN), David Andrew Neel (Zionsville, IN)
Primary Examiner: Fiona T. Powers
Attorney: Janelle D. Strode
Application Number: 8/994,445
International Classification: C07D40302;
